Nanofluidic biosensors are fluidic systems with nanometer-sized confinements and/or lateral apertures, which are used to quantify the presence of biomolecules in a solution. Most nanofluidic biosensor developments are intended for bioengineering and biotechnology applications. In the scope of this invention, the biosensors are used for example to quantify the presence of biomolecules in a solution for in vitro diagnostic applications.
Swiss patent application CH 01824/09 discloses biosensors with lateral apertures for the detection of biomolecular interactions, PCT application PCT/IB2010/050867 discloses the use of such biosensors with simple optical systems and PCT application PCT/IB2011/050979 discloses a method for avoiding long waiting times to attain stable measurement conditions. However, in all configurations described in these documents, the number of type of biomarker was limited to one per nanofluidic biosensor.
Biomarkers, also called biological markers, are substances used as specific indicators for detecting the presence of specific biomolecules. It is a characteristic that is objectively measured and evaluated as an indicator of biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.
Methods for the detection of specific biomolecules can be divided in two categories: (a) the labeled techniques and (b) the label-free techniques.
Among the labeled techniques, the widely used ones are fluorescence, colorimetry, radioactivity, phosphorescence, bioluminescence and chemiluminescence. Functionalized magnetic beads can also be considered as labeling techniques. Advantages of labeled techniques in comparison to label-free methods are the sensitivity and the molecular recognition due to specific labeling.
Among the label-free techniques, the widely used ones are electrochemical biosensors, referring to amperometric, capacitive, conductometric or impedimetric sensors, which have the advantage of being rapid and inexpensive. They measure the change in electrical properties of electrode structures as biomolecules become entrapped or immobilized onto or near the electrode. These technologies however lack molecular specific contrast, sensitivity and reliability.
Enzyme linked immunosorbent assay (ELISA) is an important biochemical technique mainly used to detect the presence of soluble biomolecules in serum, and is thus widely used as a diagnostic tool in medicine and quality control checks in various industries. ELISA analysis are however expensive, require large amounts of solution and are time consuming.
The other relevant technologies for biomolecular diagnostics are Western and Northern blots, protein electrophoresis and polymerase chain reaction (PCR). However, these methods require highly concentrated analytes and do not allow high throughput samples testing.